title: A novel recombinant DNA vaccine encoding Mycobacterium tuberculosis ESAT-6 and FL protects against Mycobacterium tuberculosis challenge in mice.
abstract: Mycobacterium tuberculosis 6-kDa early secretory antigenic target (ESAT-6) is a dominant target antigen for cell-mediated immunity in the early phase of tuberculosis. The fms-like tyrosine kinase 3 ligand (FL) that induces potent immune response has been used as an adjuvant in vaccine development. In this study, a new recombinant plasmid (pIRES-epitope-peptides-FL) encoding three T cell epitopes of ESAT-6 and FL was constructed, and the immunogenicity of the DNA vaccine was assessed in C57BL/6 mice immunized with the plasmid DNA vaccine. Additionally, a strategy of intramuscular injection with the DNA vaccine (prime) and intranasal administration of the epitope peptides (boost) was employed to induce higher immune reaction of the mice. The results showed that mice vaccinated with the recombinant plasmid DNA vaccine and boosted with the peptides not only increased the levels of Th1 cytokines (IFN-γ and IL-12), the number of IFN-γ(+) T cells and activities of cytotoxic T lymphocytes as well as IgG, but also enhanced protection against Mycobacterium tuberculosis challenge. In conclusion, these data indicate that the novel recombinant pIRES-epitope-peptides-FL plasmid is a useful DNA vaccine for preventing Mycobacterium tuberculosis infection.
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Jiang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Xia
authors.forename: Yanlai
authors.initials: Y
authors.lastname: Lu
authors.forename: Wen
authors.initials: W
authors.lastname: Qiu
authors.forename: Ganzhu
authors.initials: G
authors.lastname: Feng
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Fengxia
authors.initials: F
authors.lastname: He
authors.forename: Guangyong
authors.initials: G
authors.lastname: Peng
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Wang
keywords: Mycobacterium tuberculosis; T cell epitopes; early secretory antigenic target-6 (ESAT-6); fms-like tyrosine kinase 3 ligand (FL); recombinant plasmid